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Wilms' tumor and hypertension
Wilms’ Tumor and Hypertension By K. Sukarochana,
W. Tolentino, and W. B. Kiesewetter
W
ILMS’ TUMOR is one of the most common malignancies of childhood. It usually presents as an abdominal mass, although occasionally hematuria or pain may be the initial complaint. Traditional teaching suggests that an elevated blood pressure, with or without congestive heart failure, is rarely seen as part of the presenting picture. Because of an encounter with hypertensive congestive heart failure in 1969 in a patient with Wihns’ tumor, we reviewed a11of the patients with nephroblastomas at the Children’s Hospital of Pittsburgh to determine the incidence of blood pressure elevation. To our surprise, it was a frequent combination. Recourse to the literature also showed that arterial hypertension and Wilms’ tumor occurred more frequently than is generally appreciated. The first papers documenting this combination were by Pincoff and Bradley in the 1930s,‘*” and there have been several reports since.3-5 MATERIALS AND METHODS
All Wilms’ tumor patients seen between 1955 and 1969 were studied for the association of hypertension and the tumor. Only the 46 cases that had a complete record of blood pressures in the pre-. and postoperative periods were accepted for further analysis and review. The cut-off date of 1969 was used in order to allow at least a 2-yr follow-up for survival. The criteria of hypertension were determined by blood pressure values that were above both the systolic and diastolic pressures shown in Table 1, which was computed from data of Allen-Williams6 for children under the age of 5 yr and from data of Graham et al.7 in children over that age. The maximum blood pressure = mean blood pressure (systolic or diastolic) + standard deviation in the 95th percentile.
Case 1 R.S., a 4%yr-old white male, was evaluated because of anorexia, weakness, and weight loss for 2 mo and exertional dyspnea and restlessness for 2 wk. Physical examination revealed a cachectic, chronically ill boy with a blood pressure of 200/110 mm in both arms. A mass was palpated in the left flank, which had a murmur over it. The heart was enlarged, and a gallop rhythm and a systolic murmur were heard over the whole precordium; he was in congestive failure. An intravenous pyelogram showed the characteristic picture of Wilms’ tumor of the left kidney. An arteriogram demonstrated a mass at the lower pole of the left kidney, with marked shuntink of blood through an A-V fistula in the tumor (Fig. IA). During this procedure, renal vein samples were analyzed for plasma From the Surgical Clinic, Children’s Hospital Surgery, University of Pittsburg, Pittsburg, Pa.
of Pittsburgh,
and
the
Department
of
Presented at the Third Annual Meeting of the American Pediatric Surgical Association, Hot Springs, Vu., April 13-15, 1972. K. Sukarochana, M.D.: Clinical Assistant Professor of Pediatric Surgery, University of Pittsburgh, Associate Staff, Children’s Hospital of Pittsburgh, Pittsburgh, Pa. W. Tolentino, M.D. : Resident, Children’s Hospital of Pittsburgh, Pittsburgh, Pa. W. B. Kiesewetter, M.D.: Professor of Pediatric Surgery, University of Pittsburgh, and Surgeon-in-Chief, Children’s Hospital of Pittsburgh, Pittsburgh, Pa.
herd
of Pediatric surgery, Vol. 7, No. 5 (October-November),
1972
573
574
SUKAROCHANA, TOLENTINO. AND KIESEWETTER
renin levels, revealing 16,000 lrpg (nanograms) of renin on the involved (left) side and 10,000 ng from the right renal vein. Quantitative urinary VMA and serum catecholamines were normal. The child responded poorly to digitalization and diuretics, the blood pressure remaining elevated. At operation, a left Wilms’ tumor with A-V fistuIa was resected. When the renaI artery was occluded, the thrill in the tumor disappeared. The postoperative course was uneventful, with the blood pressure gradually returning to normal. A postoperative chest film revealed pulmonary metastases. In spite of this, the plasma renin level decreased to 220 ng within 2-3 wk. The vasculature and collecting system of the resected kidney were injected with colored plastic solutions and demonstrated an A-V malformation with distortion of a branch of the renal artery. The child received local radiation and Actinomycin in standard dosage. He is alive and free of demonstrable disease nearly 3 yr later; his blood pressure remains normal. Case
2
E.B., a 3-yr-old black male, was evaluated for abdominal distention of 9 days’ duratlon associated with fever, chills, anorexia, and cachexia. The blood pressure fluctuated but was never lower than 140/90. A firm mass was felt in the right upper quadrant. Urinary VMA and serum catecholamines were normal. The IVP was compatable with B Wilms’ tumor of the right kidney. Chest x-ray revealed a metastatic nodule in the right lung. The liver scan showed no metastasis. Surgery was delayed for 2 wk for treatment of septicemia and, ln this waiting period, the blood pressure ranged from 130/80 to 1621128. A right nephrectomy and partial right hepatectomy were done, along with excision of enlarged periaortic nodes and an omental nodule. There were several tumor nodules in the pelvis and parietal peritoneum that were not removed. Blood from the right renal vein contained 810 ng of renin, whereas blood from the inferior vena cava opposite the left renal vein revealed 466 ng. The gross specimen showed that the large Wilms’ tumor had markedly compressed the renal cortex (Fig. 1B). The nodes also contained tumor tissue. During the first 3 wk after the operation, his blood pressure went down to 102/60 mm and the renin level, as judged by peripheral venous sampling, decreased to 130 ng. Routine radiation and Actinomycin D were given. Six months after nephrectomy, the patient had an episode of intestinal obstruction from adhesive bands, which required laparotomy. At that time his blood pressure was within normal limits. Presently, he has some residual metastatic disease but is still alive and normotensive.
RESULTS
There were 82 children with Wilms’ tumor seen at the Children’s Hospital of Pittsburgh during 1955-1969. Out of this group, only 46 patients had complete records of blood pressure in the pre- and postoperative period.
Table 1. Maximum Normal Blood Pressur&‘f AgeWI
Pressure
‘12-l 1-2 2-3 3A 4-5 5 6 7
115180 123192 119185 122/84 120/80 108/84 115/84 117/54
Age (Yr) 5 9 10 11 12 13 14 15
Pressure 121/58 X3/55 125/88 128159 131/89 134/70 137/71 MO/71
575
WILM’S TUMOR AND HYPERTENSION
There were 17 who were normotensive, seven with an elevated systolic but normal diastolic pressure, and 22 hypertensive in both the systolic and diastolic phases; the incidence of concomitant tumor and hypertension, therefore, was 63%. The metastatic history and survival in this group of 46 children are shown in detail in Table 2. Nephrectomy controlled hypertension in all cases. Most of them returned to a normal level within 2-3 wk.
DISCUSSION The two cases presented showed no clinical evidence that the hypertension was due to hyperthyroidism, coarctation of the aorta, hyperactivity of the adrenal cortex, or chronic pyelonephritis. Both patients had normal catecholamine levels preoperatively, which excludes epinephrine or norepinephrine production as the cause for their hypertension. Hypertension was apparently produced by elevation of the renin level from the affected kidney. This assumption is substantiated by the effectiveness of nephrectomy in eliminating the hypertension, with the coincident return of renin levels to normal in both instances. In the first child, the renal ischemia was due to a shunting of arterial blood through a large A-V fistula in the tumor itself. This phenomenon has been described in adults with intrarenal A-V fistulas secondary to carcinoma or trauma.&” In the second case, the tumor had compressed the remaining kidney tissue within Gerota’s fascia and the renal capsule, thereby creating renal ischemia. This theory is in agreement with Hughes,3 Daniel,’ and Koons,5
Fig. 1. (A) Renal angiogram in case 1, showing early venous filling at 1 set and full venous return into IVC at 3 set, indicating an A-V fistula in the tumor. (6) Case 2, Large tumor mass in a tense capsule compressing renal cortex, which is only a thin rim at the lower pole of the kidney.
576
SUKAROCHANA, TOLENTINO, AND KIESEWETTER Table 2. Results Survivors
Metastases at Group
Normotensive Elevated systolic only Elevated Systolic/diastolic
First Operation No metastases With metastases No metastases With metastases No metastases With metastases
Total 8 9 2 4 9 13
0 yr) 8 2 2 2 8 3
Deaths
0 7 0 2 1 10
growth could encroach directly on the renal artery, or a large tumor within the renal capsule could lead to renal ischemia. Hypertension and elevated renin levels have been documented in five additional patients in our series wherein the tumors had seemingly impaired the cortical circulation and produced renal ischemia. Two of these were in very young children with mesoblastic nephromas; the remainder were in classic Wilms’ cases. In all five patients, the renin levels reverted to normal after nephrectomy. From these experiences, we suggest that hypertension in a Wilms’ tumor is the result of an elevated renin level, secondary to renal ischemia caused by pressure of the tumor directly on the renal artery, indirectly by renal compression within the capsule, or by i&arena1 A-V fistula formation. The hypothesis that Wilms’ tumor itself is capable of producing renin or an angiotensin-like substance is unlikely. I2 Seventeen of our 29 patients had metastatic disease and still were relieved of the hypertension by their nephrectomies. Further, in the two benign mesoblastic nephromas, a similar hypertension was relieved by removal of the ischemic renal tissue. As shown in Table 2, most of the survivors were among those who had no metastatic disease to begin with. The extent and persistence of metastases were the important factors in mortality. Blood pressure per se bore no relationship to the outcome of the tumor process, whether it was a systolic, or a systolic and diastolic elevation. The only death in the so-called “nonmetastatic” group was a hypertensive patient who developed pulmonary metastases 6 mo postoperatively when his blood pressure was still at the normal level attained shortly after surgery. In patients with metastatic disease, seven out of nine patients with normal blood pressures died; 12 of 17 patients with hypertension died. Thus, it seems that hypertension in the presence of a Wilms’ tumor has no bearing on survival. SUMMARY
A high percentage of Wilms’ tumor patients have hypertension associated with the tumor. Of 46 patients with complete blood pressure studies, 29 (63%) had systolic or systolic-diastolic elevations. Hypertension seems to be the result of increased renin production secondary to renal ischemia produced by the mechanical effects of the tumor. It did not, in itself, have any bearing on survival; metastatic disease was the
577
WILM’S TUMOR AND HYPERTENSION
principal factor affecting ultimate prognosis. Removal of the kidney returned blood pressure to normal in all cases, even when metastatic disease remained. REFERENCES 1. Pincoff, M. C., and Bradley, J. E.: Association of adenosarcoma of kidney (Wilms’ tumor) with arterial hypertension. Trans. Ass. Amer. Physicians 52:320,1937. 2. Bradley, J. E., and Pincoff, M. C.: The association of Adeno-myosarcoma of the kidney (Wilms’ tumor) with arterial hypertension. Ann. Intern. Med. 11:1613, 1938. 3. Hughes, J. A., Rosenblum, H., and Horn, L. G.: Hypertension in embryoma (Wilms’ tumor). Pediatrics 3:201,1949. 4. Daniel, W. E.: The hypertensive factor in Wilms’ tumor; Southern Med. J. 32:1014,1939. 5.Koons, K. M., and Ruth, M. K.: Hypertension in a 7 year old girl with Wilms’ tumor relieved by nephrectomy. JAMA 115: 1097,1940. 6. Allen-Williams, G. M.: Pulse rate and blood pressure in infancy and early childhood. Arch. Dis. Child. 20~~25,1945. 7.Graham, A. W., Hines, E. A., and Gage,
R. I’.: Blood pressure in children between the age of five and sixteen years. Amer. J. Dis. Child. 69:203,1945. 8. Jantet, G. H., Foot, E. C., and Kenyon, J. R.: Rupture of an intrarenal arteriovenous fistula secondary to carcinoma: A case report. Brit. J. Surg. 49:404,1962. 9. Scheifley, C. H.: A new clinical syndrome producing Hypertension-arteriovenous fistula of the kidney. JAMA 174:1625, 1960. 10. -, Daugherty, G. W., Greene, L. F., and Priestley, J. T.: Arteriovenous fistual of the kidney. Circulation 19:662, 1959. 11. Nicoloff, D. M.: Renal arteriovenous fistula: occurence in renal cell carcinoma. Amer. J. Surg. 108:82,1964. 12. Mitchell, J. D., Baxter, T. J., BlairWest, J. R., and McCredie, D. A.: Renin levels in nephroblastoma (Wilms’ tumor). Arch. Dis. Child. 45:376,1970.
Discussion Dr. H. Bishop (Philadelphia): I would like to quote two sentences from the most recent edition of a multiauthored textbook on pediatric surgery: “Hypertension which is consistently demonstrated in a preoperative evaluation may be taken as a bad prognostic omen. With rare exceptions there have been no long term survivors among children with Wilm’s tumor who have severe hypertension preoperatively.” The subject paper underscores the error of this quotation. I am a little concerned about the frequency of hypertension that Dr. Sukarochana reports. Even if one assumes that all the rest of their Wilms’ tumor patients who did not have blood pressures recorded in fact had normal blood pressures, the incidence is still very high at around 25%. Of course, I must ask how valid he thinks these determinations are; whether these blood pressures were taken while the child was sedated or before anesthesia, and whether they were repeated to be sure they were accurate. I discussed the findings of this paper with the National Wilms’ Tumor Study Group, which met recently, and they were very interested to learn more about the relationship of hypertension and Wilms’ tumor. They were particularly anxious to know whether arteriograms show any stenosis of the renal arteries in the patients who are hypertensive. This apparently has not been demonstrated before. They did not think that the hypertension was related to the volume of tumor. Their assumption was that the hypertension is caused by the pressure of either tumor or blood under an intact renal capsule. The National Wilms’ Tumor Study Group is going to study this problem is some depth. We are hoping that the pathologists will perhaps be able to correlate hypertension with the predominant cell type that they are now beginning to recognize. At the Children’s Hospital of Philadelphia, we have had only one case of hypertension persisting after nephrectomy for Wilms’ tumor. Curiously enough, this is a child who got too much irradiation to the opposite remaining kidney and who developed biopsy-proven
578
SUKAROCHANA, TOLENTINO, AND KIESEWETTER
radiation nephritis. This is the only explanation we can find of his persistent postoperative hypertension. Dr, Bell (Cincinnnti): I wonder if any of the children had contralateral tumors, and if the renin levels helped in detecting these tumors. Dr. M. Woo&y (Los Angeles): Please clarify the techniques used in obtaining blood for renin levels both pre- and postoperatively. Dr. Sukurochana: In answering the first question, the blood pressure on most of these patients was taken many times, and quite often it was after the preoperative medication was given. This would eliminate a high pressure from excitement. However, in some patients only one admission blood pressure was taken. The true incidence of hypertension may not be accurate in this initial study, but the occurence seems to be more frequent than we have thought in the past. We have not found renal stenosis in Wibns’ tumor demonstrated by angiogram. The obstruction of renal blood flow might be via extrinsic pressure from the enlarged lymph nodes or the tumor itself. We have not encounfered hypertension in bilateral involvement with Wilms’ tumor; however, there has been a report of recurrence of hypertension due to involvement of the remaining kidney at a later date. The blood samples for renin levels were drawn directly from the renal vein, either via percutaneous catheter under fluoroscopy, 0; by direct sampling at surgery prior to ligation of the vein. The postoperative renins were peripheral vein samples. The normal renin level is ~CO-500ng.
W. Tolentino, and W. B. Kiesewetter
W
ILMS’ TUMOR is one of the most common malignancies of childhood. It usually presents as an abdominal mass, although occasionally hematuria or pain may be the initial complaint. Traditional teaching suggests that an elevated blood pressure, with or without congestive heart failure, is rarely seen as part of the presenting picture. Because of an encounter with hypertensive congestive heart failure in 1969 in a patient with Wihns’ tumor, we reviewed a11of the patients with nephroblastomas at the Children’s Hospital of Pittsburgh to determine the incidence of blood pressure elevation. To our surprise, it was a frequent combination. Recourse to the literature also showed that arterial hypertension and Wilms’ tumor occurred more frequently than is generally appreciated. The first papers documenting this combination were by Pincoff and Bradley in the 1930s,‘*” and there have been several reports since.3-5 MATERIALS AND METHODS
All Wilms’ tumor patients seen between 1955 and 1969 were studied for the association of hypertension and the tumor. Only the 46 cases that had a complete record of blood pressures in the pre-. and postoperative periods were accepted for further analysis and review. The cut-off date of 1969 was used in order to allow at least a 2-yr follow-up for survival. The criteria of hypertension were determined by blood pressure values that were above both the systolic and diastolic pressures shown in Table 1, which was computed from data of Allen-Williams6 for children under the age of 5 yr and from data of Graham et al.7 in children over that age. The maximum blood pressure = mean blood pressure (systolic or diastolic) + standard deviation in the 95th percentile.
Case 1 R.S., a 4%yr-old white male, was evaluated because of anorexia, weakness, and weight loss for 2 mo and exertional dyspnea and restlessness for 2 wk. Physical examination revealed a cachectic, chronically ill boy with a blood pressure of 200/110 mm in both arms. A mass was palpated in the left flank, which had a murmur over it. The heart was enlarged, and a gallop rhythm and a systolic murmur were heard over the whole precordium; he was in congestive failure. An intravenous pyelogram showed the characteristic picture of Wilms’ tumor of the left kidney. An arteriogram demonstrated a mass at the lower pole of the left kidney, with marked shuntink of blood through an A-V fistula in the tumor (Fig. IA). During this procedure, renal vein samples were analyzed for plasma From the Surgical Clinic, Children’s Hospital Surgery, University of Pittsburg, Pittsburg, Pa.
of Pittsburgh,
and
the
Department
of
Presented at the Third Annual Meeting of the American Pediatric Surgical Association, Hot Springs, Vu., April 13-15, 1972. K. Sukarochana, M.D.: Clinical Assistant Professor of Pediatric Surgery, University of Pittsburgh, Associate Staff, Children’s Hospital of Pittsburgh, Pittsburgh, Pa. W. Tolentino, M.D. : Resident, Children’s Hospital of Pittsburgh, Pittsburgh, Pa. W. B. Kiesewetter, M.D.: Professor of Pediatric Surgery, University of Pittsburgh, and Surgeon-in-Chief, Children’s Hospital of Pittsburgh, Pittsburgh, Pa.
herd
of Pediatric surgery, Vol. 7, No. 5 (October-November),
1972
573
574
SUKAROCHANA, TOLENTINO. AND KIESEWETTER
renin levels, revealing 16,000 lrpg (nanograms) of renin on the involved (left) side and 10,000 ng from the right renal vein. Quantitative urinary VMA and serum catecholamines were normal. The child responded poorly to digitalization and diuretics, the blood pressure remaining elevated. At operation, a left Wilms’ tumor with A-V fistuIa was resected. When the renaI artery was occluded, the thrill in the tumor disappeared. The postoperative course was uneventful, with the blood pressure gradually returning to normal. A postoperative chest film revealed pulmonary metastases. In spite of this, the plasma renin level decreased to 220 ng within 2-3 wk. The vasculature and collecting system of the resected kidney were injected with colored plastic solutions and demonstrated an A-V malformation with distortion of a branch of the renal artery. The child received local radiation and Actinomycin in standard dosage. He is alive and free of demonstrable disease nearly 3 yr later; his blood pressure remains normal. Case
2
E.B., a 3-yr-old black male, was evaluated for abdominal distention of 9 days’ duratlon associated with fever, chills, anorexia, and cachexia. The blood pressure fluctuated but was never lower than 140/90. A firm mass was felt in the right upper quadrant. Urinary VMA and serum catecholamines were normal. The IVP was compatable with B Wilms’ tumor of the right kidney. Chest x-ray revealed a metastatic nodule in the right lung. The liver scan showed no metastasis. Surgery was delayed for 2 wk for treatment of septicemia and, ln this waiting period, the blood pressure ranged from 130/80 to 1621128. A right nephrectomy and partial right hepatectomy were done, along with excision of enlarged periaortic nodes and an omental nodule. There were several tumor nodules in the pelvis and parietal peritoneum that were not removed. Blood from the right renal vein contained 810 ng of renin, whereas blood from the inferior vena cava opposite the left renal vein revealed 466 ng. The gross specimen showed that the large Wilms’ tumor had markedly compressed the renal cortex (Fig. 1B). The nodes also contained tumor tissue. During the first 3 wk after the operation, his blood pressure went down to 102/60 mm and the renin level, as judged by peripheral venous sampling, decreased to 130 ng. Routine radiation and Actinomycin D were given. Six months after nephrectomy, the patient had an episode of intestinal obstruction from adhesive bands, which required laparotomy. At that time his blood pressure was within normal limits. Presently, he has some residual metastatic disease but is still alive and normotensive.
RESULTS
There were 82 children with Wilms’ tumor seen at the Children’s Hospital of Pittsburgh during 1955-1969. Out of this group, only 46 patients had complete records of blood pressure in the pre- and postoperative period.
Table 1. Maximum Normal Blood Pressur&‘f AgeWI
Pressure
‘12-l 1-2 2-3 3A 4-5 5 6 7
115180 123192 119185 122/84 120/80 108/84 115/84 117/54
Age (Yr) 5 9 10 11 12 13 14 15
Pressure 121/58 X3/55 125/88 128159 131/89 134/70 137/71 MO/71
575
WILM’S TUMOR AND HYPERTENSION
There were 17 who were normotensive, seven with an elevated systolic but normal diastolic pressure, and 22 hypertensive in both the systolic and diastolic phases; the incidence of concomitant tumor and hypertension, therefore, was 63%. The metastatic history and survival in this group of 46 children are shown in detail in Table 2. Nephrectomy controlled hypertension in all cases. Most of them returned to a normal level within 2-3 wk.
DISCUSSION The two cases presented showed no clinical evidence that the hypertension was due to hyperthyroidism, coarctation of the aorta, hyperactivity of the adrenal cortex, or chronic pyelonephritis. Both patients had normal catecholamine levels preoperatively, which excludes epinephrine or norepinephrine production as the cause for their hypertension. Hypertension was apparently produced by elevation of the renin level from the affected kidney. This assumption is substantiated by the effectiveness of nephrectomy in eliminating the hypertension, with the coincident return of renin levels to normal in both instances. In the first child, the renal ischemia was due to a shunting of arterial blood through a large A-V fistula in the tumor itself. This phenomenon has been described in adults with intrarenal A-V fistulas secondary to carcinoma or trauma.&” In the second case, the tumor had compressed the remaining kidney tissue within Gerota’s fascia and the renal capsule, thereby creating renal ischemia. This theory is in agreement with Hughes,3 Daniel,’ and Koons,5
Fig. 1. (A) Renal angiogram in case 1, showing early venous filling at 1 set and full venous return into IVC at 3 set, indicating an A-V fistula in the tumor. (6) Case 2, Large tumor mass in a tense capsule compressing renal cortex, which is only a thin rim at the lower pole of the kidney.
576
SUKAROCHANA, TOLENTINO, AND KIESEWETTER Table 2. Results Survivors
Metastases at Group
Normotensive Elevated systolic only Elevated Systolic/diastolic
First Operation No metastases With metastases No metastases With metastases No metastases With metastases
Total 8 9 2 4 9 13
0 yr) 8 2 2 2 8 3
Deaths
0 7 0 2 1 10
growth could encroach directly on the renal artery, or a large tumor within the renal capsule could lead to renal ischemia. Hypertension and elevated renin levels have been documented in five additional patients in our series wherein the tumors had seemingly impaired the cortical circulation and produced renal ischemia. Two of these were in very young children with mesoblastic nephromas; the remainder were in classic Wilms’ cases. In all five patients, the renin levels reverted to normal after nephrectomy. From these experiences, we suggest that hypertension in a Wilms’ tumor is the result of an elevated renin level, secondary to renal ischemia caused by pressure of the tumor directly on the renal artery, indirectly by renal compression within the capsule, or by i&arena1 A-V fistula formation. The hypothesis that Wilms’ tumor itself is capable of producing renin or an angiotensin-like substance is unlikely. I2 Seventeen of our 29 patients had metastatic disease and still were relieved of the hypertension by their nephrectomies. Further, in the two benign mesoblastic nephromas, a similar hypertension was relieved by removal of the ischemic renal tissue. As shown in Table 2, most of the survivors were among those who had no metastatic disease to begin with. The extent and persistence of metastases were the important factors in mortality. Blood pressure per se bore no relationship to the outcome of the tumor process, whether it was a systolic, or a systolic and diastolic elevation. The only death in the so-called “nonmetastatic” group was a hypertensive patient who developed pulmonary metastases 6 mo postoperatively when his blood pressure was still at the normal level attained shortly after surgery. In patients with metastatic disease, seven out of nine patients with normal blood pressures died; 12 of 17 patients with hypertension died. Thus, it seems that hypertension in the presence of a Wilms’ tumor has no bearing on survival. SUMMARY
A high percentage of Wilms’ tumor patients have hypertension associated with the tumor. Of 46 patients with complete blood pressure studies, 29 (63%) had systolic or systolic-diastolic elevations. Hypertension seems to be the result of increased renin production secondary to renal ischemia produced by the mechanical effects of the tumor. It did not, in itself, have any bearing on survival; metastatic disease was the
577
WILM’S TUMOR AND HYPERTENSION
principal factor affecting ultimate prognosis. Removal of the kidney returned blood pressure to normal in all cases, even when metastatic disease remained. REFERENCES 1. Pincoff, M. C., and Bradley, J. E.: Association of adenosarcoma of kidney (Wilms’ tumor) with arterial hypertension. Trans. Ass. Amer. Physicians 52:320,1937. 2. Bradley, J. E., and Pincoff, M. C.: The association of Adeno-myosarcoma of the kidney (Wilms’ tumor) with arterial hypertension. Ann. Intern. Med. 11:1613, 1938. 3. Hughes, J. A., Rosenblum, H., and Horn, L. G.: Hypertension in embryoma (Wilms’ tumor). Pediatrics 3:201,1949. 4. Daniel, W. E.: The hypertensive factor in Wilms’ tumor; Southern Med. J. 32:1014,1939. 5.Koons, K. M., and Ruth, M. K.: Hypertension in a 7 year old girl with Wilms’ tumor relieved by nephrectomy. JAMA 115: 1097,1940. 6. Allen-Williams, G. M.: Pulse rate and blood pressure in infancy and early childhood. Arch. Dis. Child. 20~~25,1945. 7.Graham, A. W., Hines, E. A., and Gage,
R. I’.: Blood pressure in children between the age of five and sixteen years. Amer. J. Dis. Child. 69:203,1945. 8. Jantet, G. H., Foot, E. C., and Kenyon, J. R.: Rupture of an intrarenal arteriovenous fistula secondary to carcinoma: A case report. Brit. J. Surg. 49:404,1962. 9. Scheifley, C. H.: A new clinical syndrome producing Hypertension-arteriovenous fistula of the kidney. JAMA 174:1625, 1960. 10. -, Daugherty, G. W., Greene, L. F., and Priestley, J. T.: Arteriovenous fistual of the kidney. Circulation 19:662, 1959. 11. Nicoloff, D. M.: Renal arteriovenous fistula: occurence in renal cell carcinoma. Amer. J. Surg. 108:82,1964. 12. Mitchell, J. D., Baxter, T. J., BlairWest, J. R., and McCredie, D. A.: Renin levels in nephroblastoma (Wilms’ tumor). Arch. Dis. Child. 45:376,1970.
Discussion Dr. H. Bishop (Philadelphia): I would like to quote two sentences from the most recent edition of a multiauthored textbook on pediatric surgery: “Hypertension which is consistently demonstrated in a preoperative evaluation may be taken as a bad prognostic omen. With rare exceptions there have been no long term survivors among children with Wilm’s tumor who have severe hypertension preoperatively.” The subject paper underscores the error of this quotation. I am a little concerned about the frequency of hypertension that Dr. Sukarochana reports. Even if one assumes that all the rest of their Wilms’ tumor patients who did not have blood pressures recorded in fact had normal blood pressures, the incidence is still very high at around 25%. Of course, I must ask how valid he thinks these determinations are; whether these blood pressures were taken while the child was sedated or before anesthesia, and whether they were repeated to be sure they were accurate. I discussed the findings of this paper with the National Wilms’ Tumor Study Group, which met recently, and they were very interested to learn more about the relationship of hypertension and Wilms’ tumor. They were particularly anxious to know whether arteriograms show any stenosis of the renal arteries in the patients who are hypertensive. This apparently has not been demonstrated before. They did not think that the hypertension was related to the volume of tumor. Their assumption was that the hypertension is caused by the pressure of either tumor or blood under an intact renal capsule. The National Wilms’ Tumor Study Group is going to study this problem is some depth. We are hoping that the pathologists will perhaps be able to correlate hypertension with the predominant cell type that they are now beginning to recognize. At the Children’s Hospital of Philadelphia, we have had only one case of hypertension persisting after nephrectomy for Wilms’ tumor. Curiously enough, this is a child who got too much irradiation to the opposite remaining kidney and who developed biopsy-proven
578
SUKAROCHANA, TOLENTINO, AND KIESEWETTER
radiation nephritis. This is the only explanation we can find of his persistent postoperative hypertension. Dr, Bell (Cincinnnti): I wonder if any of the children had contralateral tumors, and if the renin levels helped in detecting these tumors. Dr. M. Woo&y (Los Angeles): Please clarify the techniques used in obtaining blood for renin levels both pre- and postoperatively. Dr. Sukurochana: In answering the first question, the blood pressure on most of these patients was taken many times, and quite often it was after the preoperative medication was given. This would eliminate a high pressure from excitement. However, in some patients only one admission blood pressure was taken. The true incidence of hypertension may not be accurate in this initial study, but the occurence seems to be more frequent than we have thought in the past. We have not found renal stenosis in Wibns’ tumor demonstrated by angiogram. The obstruction of renal blood flow might be via extrinsic pressure from the enlarged lymph nodes or the tumor itself. We have not encounfered hypertension in bilateral involvement with Wilms’ tumor; however, there has been a report of recurrence of hypertension due to involvement of the remaining kidney at a later date. The blood samples for renin levels were drawn directly from the renal vein, either via percutaneous catheter under fluoroscopy, 0; by direct sampling at surgery prior to ligation of the vein. The postoperative renins were peripheral vein samples. The normal renin level is ~CO-500ng.